Pregnant women with polycystic ovary syndrome assigned to metformin therapy for the duration of pregnancy were less likely to experience a late-term miscarriage or preterm birth when compared with similar women assigned to placebo, according to findings published in The Lancet Diabetes & Endocrinology.

“The results of PregMet2 showed a nonsignificant reduction in the incidence of late miscarriage or preterm delivery — however, this difference was significant in a post-hoc pooled analysis of individual participant data including our two previous trials,” Tone S. Løvvik, PhD, of the department of clinical and molecular medicine at the Norwegian University of Science and Technology in Trondheim, Norway, and colleagues wrote in the study background. “Notably, metformin had no effect on the incidence of gestational diabetes or the need for insulin treatment.”

Løvvik and colleagues analyzed data from 487 pregnant women with a diagnosis of PCOS (according to Rotterdam criteria) recruited from 14 hospitals in Iceland, Norway and Sweden as part of the PregMet2 study. Between October 2012 and September 2017, researchers randomly assigned women to twice-daily metformin (n = 244) or placebo (n = 243) from week 2 until delivery. Primary outcome was the composite incidence of late miscarriage (between 13 and 22 weeks’ gestation) and preterm birth (between 23 and 26 weeks’ gestation). Secondary endpoints included incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension and admission of the infant to the neonatal ICU.

In the intention-to-treat analysis, the composite primary outcome of late miscarriage and preterm birth occurred in 12 women in the metformin group (5%) and 23 women in the placebo group (10%), for an OR of 0.5 (95% CI, 0.22-1.08). Researchers did not observe a between-group difference with respect to developing gestational diabetes, which was diagnosed in 60 women in the metformin group (25%) and 57 women in the placebo group (24%; OR = 1.06; 95% CI, 0.68-1.64). Nine women in each group required insulin therapy, according to researchers.

Researchers did not observe any between-group differences in serious adverse events in mothers or offspring, and no serious adverse events were considered to be drug-related.

“Metformin had no effect on the development or severity of gestational diabetes, although it led to reduced weight gain compared with placebo,” the researchers wrote. “There is, therefore, no evidence to recommend metformin as prevention or treatment for gestational diabetes in women with PCOS. However, metformin did reduce late miscarriage and preterm birth.”

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The researchers noted that, due to the increased risk for pregnancy complications and the high prevalence of comorbidities in pregnant women with PCOS, intensive surveillance of pregnant women with PCOS is necessary. – by Regina Schaffer

Disclosure: One of the study authors reports he has received personal fees for teaching and participating in a review board panel for Bayer and Gedeon Richter.